Evidence map›Paper›PMID 25907691›Full record

ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2015

The small molecule ferristatin II induces hepatic hepcidin expression in vivo and in vitro.

Ahmed A Alkhateeb, Peter D Buckett, Andrew M Gardeck, Jonghan Kim, Shaina L Byrne, Paula G Fraenkel, Marianne Wessling-Resnick

Abstract read
In one paragraph

Article in American journal of physiology. Gastrointestinal and liver physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
2.3field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Targeting iron metabolism in drug discovery and delivery.Nature reviews. Drug discovery · 2017
    Review
  6. Developing drugs targeting transition metal homeostasis.Current opinion in chemical biology · 2017
    Review
  7. Anemia of Inflammation: A Review.The Medical clinics of North America · 2017
    Review
  8. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Ahmed A AlkhateebDepartment of Genetic and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts;
Peter D BuckettDepartment of Genetic and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts;
Andrew M GardeckDepartment of Genetic and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts;
Jonghan KimDepartment of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts; and.
Shaina L ByrneDepartment of Genetic and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts;
Paula G FraenkelDivision of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
Marianne Wessling-ResnickDepartment of Genetic and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts; wessling@hsph.harvard.edu.
Harvard University · USBeth Israel Deaconess Medical Center · USNortheastern University · US

Funding

STRUCTURE-FUNCTION RELATIONSHIPS IN THE ALIMENTARY TRACTP30DK034854 · NIDDK · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI JONATHAN C KAGAN · 1986 to 2026
$32.4M
Microgial Iron Metabolism and Its Regulation by CannabinoidsR01DK064750 · NIDDK · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI LEE, CHIH-HAO · 2004 to 2021
$4.2M
Interdisciplinary Training in Genes and the EnvironmentT32ES016645 · NIEHS · HARVARD SCHOOL OF PUBLIC HEALTH · PI LEE, CHIH-HAO · 2008 to 2018
$4.0M
An integrated molecular approach to understand variation in iron metabolismR01GM083198 · NIGMS · UNIVERSITY OF FLORIDA · PI VULPE, CHRISTOPHER D · 2012 to 2015
$2.7M
Modifiers of hepcidin expression as new therapies for iron overloadR01DK085250 · NIDDK · BETH ISRAEL DEACONESS MEDICAL CENTER · PI FRAENKEL, PAULA GOODMAN · 2011 to 2015
$1.9M
NIDDK NIH HHS P30 DK034854NIDDK NIH HHS R01 DK064750NIDDK NIH HHS R01DK064750NIDDK NIH HHS R01 DK085250NIDDK NIH HHS R01DK085250NIEHS NIH HHS T32 ES016645NIGMS NIH HHS R01 GM083198NIGMS NIH HHS R01GM083198
6 · The paper itself

Abstract

Previous studies have shown that administration of ferristatin II to rats is associated with decreased serum iron, reduced transferrin saturation, and increased hepatic hepcidin expression. BMP and IL-6 signaling act via Smad and Stat3 transcription factors, respectively, to increase expression of hepcidin, the master regulator of iron metabolism. In this study, we aimed to explore the underlying mechanism of ferristatin II action on hepcidin production. We found that ferristatin II greatly increased hepcidin expression both in vivo and in vitro. In the rat liver, ferristatin II treatment decreased expression of Smad downstream targets Smad7 and Id1 and increased expression of Stat3 downstream targets α-2-macroglobulin, α-1-acid glycoprotein, and C-reactive peptide. Ferristatin II also increased Stat3 phosphorylation in the rat liver without affecting serum or hepatic IL-6 levels. It is unclear whether the Stat3 activation observed in vivo is a cause or a consequence to hepcidin induction. Reporter gene expression studies demonstrated that ferristatin II synergized with BMP6 and IL-6 to enhance hepcidin expression in vitro. However, this synergy was not due to activation of either Smad or Stat3 signaling, raising the possibility that ferristatin II may activate a novel pathway for hepcidin regulation.

Indexed as

AnimalsAntimicrobial Cationic PeptidesBiphenyl CompoundsBone Morphogenetic Protein 6HepcidinsHumansInterleukin-6LiverMembrane ProteinsPhosphorylationRats, Sprague-DawleySignal TransductionSTAT3 Transcription FactorSulfonesAntimicrobial Cationic PeptidesBiphenyl CompoundsBone Morphogenetic Protein 6ferristatin IIHepcidinsInterleukin-6Membrane ProteinsSTAT3 Transcription FactorSulfonesBMP6hemochromatosisIL-6iron transport

Identifiers

PMID25907691
PMCPMC4469869
OpenAlexW2011517294

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.